Evidence map›Paper›PMID 29720183›Full record

ArticleJournal of biomedical science2018

Disrupted sphingolipid metabolism following acute clozapine and olanzapine administration.

Katrina Weston-Green, Ilijana Babic, Michael de Santis, Bo Pan, Magdalene K Montgomery, Todd Mitchell, Xu-Feng Huang, Jessica Nealon

Open access · diamondAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of biomedical science, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
2.4field-weighted citation impact, top 11% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

17 citing papers in PubMed, 32 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 3 institutions in 2 countries.

Katrina Weston-GreenCentre for Medical and Molecular Biosciences, and School of Medicine, Faculty of Science, Medicine and Health, University of Wollongong, Wollongong, NSW, 2522, Australia. katrina_green@uow.edu.au.ORCID http://orcid.org/0000-0002-4521-8463
Ilijana BabicCentre for Medical and Molecular Biosciences, and School of Medicine, Faculty of Science, Medicine and Health, University of Wollongong, Wollongong, NSW, 2522, Australia.
Michael de SantisCentre for Medical and Molecular Biosciences, and School of Medicine, Faculty of Science, Medicine and Health, University of Wollongong, Wollongong, NSW, 2522, Australia.
Bo PanDepartment of Pharmacy, Yangzhou University Medical Academy, Yangzhou, 225001, Jiangsu, China.
Magdalene K MontgomeryDepartment of Physiology, School of Biomedical Sciences, Monash University, Clayton, VIC, 3800, Australia.
Todd MitchellCentre for Medical and Molecular Biosciences, and School of Medicine, Faculty of Science, Medicine and Health, University of Wollongong, Wollongong, NSW, 2522, Australia.
Xu-Feng HuangCentre for Medical and Molecular Biosciences, and School of Medicine, Faculty of Science, Medicine and Health, University of Wollongong, Wollongong, NSW, 2522, Australia.
Jessica NealonIllawarra Health and Medical Research Institute, Wollongong, NSW, 2522, Australia.
University of Wollongong · AUMonash University · AUYangzhou University · CN

Funding

University of Wollongong University Research Council Small Project Grant
6 · The paper itself

Abstract

backgroundSecond generation antipsychotics (SGAs) induce glucometabolic side-effects, such as hyperglycemia and insulin resistance, which pose a therapeutic challenge for mental illness. Sphingolipids play a role in glycaemic balance and insulin resistance. Endoplasmic reticulum (ER) stress contributes to impaired insulin signalling and whole-body glucose intolerance. Diabetogenic SGA effects on ER stress and sphingolipids, such as ceramide and sphingomyelin, in peripheral metabolic tissues are unknown. This study aimed to investigate the acute effects of clozapine and olanzapine on ceramide and sphingomyelin levels, and protein expression of key enzymes involved in lipid and glucose metabolism, in the liver and skeletal muscle.

methodsFemale rats were administered olanzapine (1 mg/kg), clozapine (12 mg/kg), or vehicle (control) and euthanized 1-h later. Ceramide and sphingomyelin levels were examined using electrospray ionization (ESI) mass spectrometry. Expression of lipid enzymes (ceramide synthase 2 (CerS2), elongation of very long-chain fatty acid 1 (ELOVL1), fatty acid synthase (FAS) and acetyl CoA carboxylase 1 (ACC1)), ER stress markers (inositol-requiring enzyme 1 (IRE1) and eukaryotic initiation factor (eIF2α) were also examined.

resultsClozapine caused robust reductions in hepatic ceramide and sphingolipid levels (p < 0.0001), upregulated CerS2 (p < 0.05) and ELOVL1 (+ 37%) and induced significant hyperglycemia (vs controls). In contrast, olanzapine increased hepatic sphingomyelin levels (p < 0.05 vs controls). SGAs did not alter sphingolipid levels in the muscle. Clozapine increased (+ 52.5%) hepatic eIF2α phosphorylation, demonstrating evidence of activation of the PERK/eIF2α ER stress axis. Hepatic IRE1, FAS and ACC1 were unaltered.

conclusionsThis study provides the first evidence that diabetogenic SGAs disrupt hepatic sphingolipid homeostasis within 1-h of administration. Sphingolipids may be key candidates in the mechanisms underlying the diabetes side-effects of SGAs; however, further research is required.

Indexed as

AnimalsAntipsychotic AgentsBenzodiazepinesCeramidesClozapineFemaleGene ExpressionGlucoseLiverMuscle, SkeletalOlanzapineRatsRats, Sprague-DawleySphingomyelinsAntipsychotic AgentsBenzodiazepinesCeramidesClozapineGlucoseOlanzapineSphingomyelinsAntipsychoticCeramideER stressHyperglycemiaSphingolipidSphingomyelin

Identifiers

PMID29720183
PMCPMC5932814
OpenAlexW2806787626

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.